Whole Transcriptome Analysis of Breast Cancer Tumors during Neoadjuvant Chemotherapy: Association with Hematogenous Metastasis

The assessment of molecular genetic landscape changes during NAC and the relationship between molecular signatures in residual tumors are promising approaches for identifying effective markers of outcome in breast cancer. The majority of the data in the literature present the relationship between the molecular genetic landscape and the response to NAC or are simply descriptive. The present study aimed to determine changes in expression profiles during NAC and assess the relationship between gene expression and the outcome of patients with luminal B HER2 breast cancer depending on distant hematogenous metastasis. The study included 39 patients with luminal B HER2-BC. The patients received 6–8 courses of NAC, and paired samples consisting of biopsy and surgical materials were analyzed. A full transcriptome microarray analysis was performed using the human Clariom™ S Assay platform (Affymetrix, 3450 Central Expy, Santa Clara, CA, 95051, USA). A comparison of the expression profiles of patients with breast cancer before and after NAC, depending on the status of hematogenous metastasis, was conducted. It was shown that the amount of DEGs in the tumor was reduced by more than six times after NAC. The top 10 signaling pathways were also found, the activity of which varied depending on the status of hematogenous metastasis before and after NAC. In addition, the association of DEGs with hematogenous metastasis in patients with breast cancer was evaluated: MFS was assessed depending on the expression level of 21 genes. It was shown that MFS was significantly associated with the expression level and pattern of nine genes. The expression levels of nine DEGs in the tumors of patients with breast cancer after NAC were significantly correlated with MFS when the status of hematogenous metastasis was taken into account.